Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial cells (IECs) and the interior of gut-associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian immune system and collectively influence intestinal immune cell homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial-associated, or (iii) lymphoid tissue-resident, and we discuss the role and regulation of these microbial populations in health and disease.

Commensal bacteria in the mammalian GI tract can be classified by their anatomical localization as (i) luminal, (ii) epithelial-associated or (iii) lymphoid tissue-resident. Commensal bacteria are important for promoting normal host physiology. In the healthy mammals, most commensal bacteria occupy the lumen of the intestine while some are found associated with the intestinal epithelium. Recent studies have identified that commensal bacteria can also inhabit gut-associated lymphoid tissues in the steady state.

Colonization of the mammalian GI tract by epithelial-associated commensal bacteria promotes pro-inflammatory immune responses and is regulated by distinct host mechanisms. SFB is a model epithelial-associated commensal bacterium that colonizes the small intestine by adhering to IECs. SFB can promote pro-inflammatory immune responses that are associated with both pathogen immunity and autoimmunity. Some members of the luminal commensal flora such as B. fragilis and Clostridia can also colonize the epithelial surface of the colon and may interact with IECs.